1B), whereas the development of anemia (hemoglobin <100

g/L) occurred gradually over the course of treatment (Fig. 1C). The baseline demographics of patients who developed anemia compared with those who did not are shown in Table 1. Patients who developed anemia were more likely to be female and significantly older with lower body weight, body mass index, creatinine clearance, hemoglobin levels, white cell counts and platelet counts than patients who did not become anemic. Patients with hemoglobin decline >30 g/L were more likely to be older, female, and with lower body weight and higher baseline NVP-AUY922 in vivo hemoglobin than patients with a maximal hemoglobin decline ≤30 g/L (data not shown). The allocated and mean dosages received for PEG-IFN and ribavirin at weeks 12, 24, and 48 of therapy are shown in Table 2. At baseline, more patients who became anemic were allocated a lower dose of ribavirin (1,000 mg versus 1,200 mg) than patients who did not become anemic (61% versus 44%; P = 0.0002). The mean daily ribavirin dosage was significantly lower in patients who developed anemia compared with those who did not become anemic at week 12 (998 ± 143 mg/day versus 1,052 ± 152 mg/day; P = 0.0001) and week 24 (967 ± 169

mg/day versus 1030 ± 210 mg/day; P = 0.0002); there was no significant difference in ribavirin exposure at week 48. The mean weekly PEG-IFN dosage at week 48 was significantly lower in patients who did not become anemic compared with anemic patients for both standard and induction FK506 therapy arms; there was no significant difference

in PEG-IFN exposure at earlier times. Similar outcomes were observed when PEG-IFN and ribavirin exposure were analyzed as a percentage of planned target dose (data not shown). Virological responses at the end of treatment (ETR) and at the end of follow-up (SVR) were significantly different between patients with hemoglobin <100 g/L at any time during treatment compared with those with hemoglobin ≥100 g/L (ETR, 80% versus 65%, respectively, P = 0.003; SVR, 61% versus 50%, respectively, P = 0.02). Relapse rates were similar, however (Fig. 2A). Similarly, ETR and SVR rates were significantly higher in patients with hemoglobin decline >30 g/L compared with those 3-oxoacyl-(acyl-carrier-protein) reductase with hemoglobin decline ≤30 g/L. An ETR occurred in 72% of patients with a hemoglobin decline >30 g/L compared with 52% of those without a similar change in hemoglobin (P < 0.001). Similarly, a SVR occurred in 54% with a hemoglobin decline >30 g/L compared with 46% with a hemoglobin decline ≤30 g/L (P = 0.049). Relapse rates were similar (Fig. 2B). In separate multiple logistic regression analyses, both hemoglobin <100 g/L (protocol defined anemia) and maximum hemoglobin decline >30 g/L during treatment were significantly associated with SVR rate. The odds ratio estimate for SVR for hemoglobin <100 g/L was 1.97 (95% confidence interval, 1.08-3.62; P = 0.028). The odds ratio estimate for hemoglobin decline >30 g/L was 2.17 (95% confidence interval, 1.31-3.